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Sato M, Todoriki S, Takahashi T, et al. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats. J Toxicol Pathol. 2015;28(2):99-107doi: 10.1293/tox.2015-0002.
Sato, M., Todoriki, S., Takahashi, T., Hafez, E., Takasu, C., Uehara, H., Yamakage, K., Kondo, T., Matsumoto, K., Furuta, M., & Izumi, K. (2015). Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats. Journal of toxicologic pathology, 28(2), 99-107. https://doi.org/10.1293/tox.2015-0002
Sato, Makoto, et al. "Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats." Journal of toxicologic pathology vol. 28,2 (2015): 99-107. doi: https://doi.org/10.1293/tox.2015-0002
Sato M, Todoriki S, Takahashi T, Hafez E, Takasu C, Uehara H, Yamakage K, Kondo T, Matsumoto K, Furuta M, Izumi K. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats. J Toxicol Pathol. 2015 Apr;28(2):99-107. doi: 10.1293/tox.2015-0002. Epub 2015 Feb 16. PMID: 26028819; PMCID: PMC4444508.
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J Toxicol Pathol. 2015 Apr;28(2):99-107. doi: 10.1293/tox.2015-0002. Epub 2015 Feb 16.

Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats.

Journal of toxicologic pathology

Makoto Sato, Setsuko Todoriki, Tetsuyuki Takahashi, Ezar Hafez, Chie Takasu, Hisanori Uehara, Kohji Yamakage, Takashi Kondo, Kozo Matsumoto, Masakazu Furuta, Keisuke Izumi

Affiliations

  1. Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
  2. Food Safety Division, National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan.
  3. Division of Alternative Toxicology Test, Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan.
  4. Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
  5. Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama Kamigamo, Kita-ku, Kyoto 603-8555, Japan.
  6. Laboratory of Quantum-beam Chemical Biology, Radiation Research Center, Osaka Prefecture University, 1-2 Gakuen-cho, Sakai, Osaka 599-8570, Japan.

PMID: 26028819 PMCID: PMC4444508 DOI: 10.1293/tox.2015-0002

Abstract

A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females.

Keywords: 2-tetradecylcyclobutanone; 90-day oral toxicity; colon carcinogenesis; food irradiation

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